Hyperglycemia and hypercholesterolemia are major health concerns. Hyperglycemia can be due to diabetes, of which there are two major types—insulin dependent diabetes mellitus (IDDM), or type I diabetes, and non-insulin dependent diabetes mellitus (NIDDM), or type II diabetes. IDDM, or juvenile onset diabetes, is found mostly in young patients and is believed to be caused by genetically destructive mechanisms involving circulating antibodies to insulin which are aggravated by external factors such as infection (viruses, etc.), toxic chemicals, etc. As the name suggests, insulin is required for the treatment of IDDM.
NIDDM, or maturity onset diabetes, is more common than IDDM, and occurs mostly in adults, either obese or non-obese. In NIDDM there is a deficiency of insulin secretion or action. This deficiency may be due to down regulation of insulin receptors, decreased sensitivity to insulin action or a post receptor defect in which the insulin signal is inefficiently or improperly transduced. About 70% of diabetics have NIDDM and require oral antidiabetic drugs, either alone or in combination with insulin.
Insulin is typically required to be injected and is used for diabetics with insulinopenia who do not respond to diet, oral drugs, or both. Some of the possible side effects of insulin use are insulin antibody formation, insulin resistance, or allergic symptoms. Oral drugs for diabetes are generally of two types: biguanides and sulphonylureas. These drugs are referred to as hypoglycemic drugs because they decrease blood glucose levels in diabetic patients. Oral drugs differ from insulin in their chemical structure and their mechanism of action.
Their primary mechanism of blood glucose-lowering action is extra-pancreatic, i.e., they function by increasing the utilization of glucose in tissues (e.g., liver and muscle), decreasing the formation of glucose (gluconeogenesis) in liver, and reducing the absorption of glucose from intestines. The increased utilization of glucose caused by biguanide drugs, especially phenformin, produces lactic acid which can cause lactic acidosis, a serious side effect. For this and other reasons, phenformin has been discontinued from use in some countries, but is used occasionally in some other countries.
Particular examples of earlier sulphonylureas are tolbutamide (orinase), chlorpropamide, acetohexamide (dymelor), and tolazamide (tolinase). Their primary mechanism of action is to increase the release of insulin from the pancreatic beta cells in the islets of Langerhans, which, in turn, reduces blood glucose levels. Sulphonylureas are also known to act on tissues other than the pancreas (extrapancreatic effect), like the liver. Many of these drugs have been replaced by more potent second-generation sulphonylureas, like glibenclamide, gliclazide, glitazones and glipizide. The latter drug has a longer duration of action, up to 24 hours.
Because of its higher potency, glibenclamide treatment frequently produces hypoglycemia (decrease in blood glucose level below normal). Furthermore, second-generation sulphonylureas also produce serious side effects including myocarditis (in some obese diabetics), hyponatremia, transient leukopenia, and thrombocytopenia. Long-term use of these drugs over a number of years, taken daily or more than once in a day, is associated with hypoglycemia or hyperglycemia, diabetic ketoacidosis, and may cause coma, allergic reactions, leukopenia, skin and gastrointestinal disturbances and predispose to coronary artery disease. Furthermore, long-term use often necessitates increased doses to achieve efficacy. Daily injection of insulin, besides being painful, may cause depression and other psychological problems.
Hypercholesterolemia can lead to cardiovascular disease (CVD) which accounts for a major proportion (23%) of all deaths. Atherosclerosis, together with its other complications, is the pathological process that underlies the majority of coronary heart diseases (CHD). Atherosclerosis is also responsible for thrombotic and embolic strokes, aortic aneurymal disease, renovascular hypertension, peripheral vascular diseases, and other clinical syndromes. Therefore, prevention of atherosclerosis is of paramount importance for increasing human life span and for improving health.
Dietary habits contribute to the increased incidence of coronary and other atherosclerotic diseases. In particular, the intake of saturated fat and cholesterol (Stamler et al., 1988, Arch. Pathol. Lab. Med. 112:1032) along with high calories, as well as a low fiber intake lead to high levels of total serum cholesterol and its atherogenic subfractions (low-density lipoproteins (LDL) and very low density lipoproteins (VLDL)), and to high prevalence and incidence rates of hypercholesterolemia. Increased serum cholesterol is one of the major etiologically significant risk factors for CHD and other atherosclerotic diseases.
Trigonella foenumgraecum Linn, commonly known as fenugreek, belongs to the family Papilinaceae Leguminosae. It is an annual herb growing to a height of about one foot. The seeds of this plant are used as spice in India and many other countries. Fenugreek seeds are 2-5 mm long and 2-6 mm broad with yellowish brown color and have a furrow on both sides (see FIG. 1). The seeds contain proteins (13%), fat (26%), fiber (46%), carbohydrates (7%), vitamins (3%) mostly carotene, thiamine, riboflavin and nicotinic acid, minerals (4%) and other saponins (steroidal & non steroidal).
Medicinal properties have been attributed to this plant. Administration of whole seed powder purportedly prevented hyperglycemia induced by cadmium and alloxan in rats. T. Ghafghazi et al., Shiraz Med. J., 8, 14-25 (1977). Powder from seeds taken every day for 10 days reduced fasting blood glucose levels and improved glucose tolerance in Type I diabetic patients. R. D. Sharma et al., Eur. J. Clin. Nutr., 44(4), 301-306 (1990). Seed powder was also asserted to have hypocholesterolemic effect. Y. Sauvaire et al., Lipids, 26(3), 191-197 (1991). These hypoglycemic and hypocholesterolemic activities have been attributed to either fiber or saponins. Coumarin, a minor component of fenugreek seeds, showed hypoglycemic effect; however, coumarin is toxic at all doses tested. Decoction of the seeds (boiling in water) purportedly improved severe diabetes and cured milder diabetes in humans. M. Moissides et al., Janus 43, 129-13 (1979).